Hypertension is known to be a disease which causes, as a complication, stroke or heart trouble which ranks high in the list of death cause in Japan, so that various studies have been made for the prevention and treatment thereof. The system for regulating the blood pressure is complicated and therefore, various types of antihypertensives have been used.
Such antihypertensives include diuretics, .beta.-blockers and ACE inhibitors. However, the diuretics cause, as an adverse effect, hyperuricemia, worsening of diabetes metlitus, induction of gouty attack or the like; the .beta.-blockers heart failure, bronchospasm or the like; and the ACE inhibitors dyspnea, cardioinihibition or the like. Thus, the antihypertensives of the prior art respectively cause serious adverse effects, particularly heart troubles, being disadvantageously difficult to use.
In Japan, the number of patients with coronary failures has reached the same level as that of the European and American countries with the westernization of the life style, and it is presumed that there are a considerably large number of patients with ischemic heart diseases (such as angina pectoris or myocardial infarction) including those induced from hypertension.
Although nitrite preparations and .beta.-blockers have been used as a preventive and therapeutic agent for angina pectoris, the nitrite preparations are disadvantageous in that they induce a tolerance in the patients and cause an adverse effect such as methemoglobinemia or ocular hypertension, while the .beta.-blockers cause, as described above, an adverse effect such as heart failure or bronchospasm. Therefore, discretion must be used in the administration of the drugs.
Meanwhile, the number of patients with asthma has recently increased, presumably owing to changes in the dietary habits or the worsening of the living environment by environmental pollution or the like.
Up to this time, .beta.-stimulants, methylxanthines, mast cell stabilizers and steroids have been used as preventive and therapeutic agents for asthma. However, the .beta.-stimulants cause, as an adverse effect, arrhythmia, hypertension, headache or the like; the methylxanthines gastrointestinal troubles or neuropathy; and the steroids diabetes mellitus or osteoporosis. Thus, these drugs sometimes cause serious adverse effects, so that discretion must be used in the administration thereof. Although, the mast cell stabilizers do not cause any serious adverse effect, they have disadvantages that the administration thereof to children or the aged is difficult, because they can be administered only as an inhalant, that they are inefficacious against serious asthma, that the efficacy thereof is poor, and that they cannot be used but as a preventive.
Under these circumstances, it has still been desired to develop a hypotensive or a preventive and therapeutic agent for heart diseases or asthma which has various mechanisms of action and is easily administrable by virtue of its higher safeness and superior to those of the prior art.
The inventors of the present invention have made intensive studies on compounds useful as such drugs. As a result of the studies, they have directed their attention to an ATP-sensitive potassium channel opening activity and have started studies for the purpose of finding a compound having such an activity.
As a result of these studies, the inventors of the present invention have found that thioformamide derivatives which will be described below can attain the above object. The present invention has been accomplished on the basis of this finding.
Although thioformamide derivatives having an activity as a drug are disclosed in, e.g., Japanese Patent Publication No. 59150/1990 and Japanese Patent Laid-Open Nos. 63260/1991, 289543/1990, 286659/1990, 211566/1989, 278/1990, 308275/1989 and 258760/1990, the compounds of the present invention are different from them in the structures.